Genetics & Family History
The majority of colon cancer patients do not have a family history or genetic connection to the disease. This is when the cancer occurs by chance, and is often called “sporadic cancer.”
However, in some families, we see more cancer than we would expect. About one in four patients have a family history of colon cancer that could suggest a genetic and/or hereditary factor. A family history of colon cancer, that is, an immediate family member (parent, brother, sister) or multiple family members with colon cancer or polyps, puts you at an increased risk for the disease.
If you have a family history, you may need to be screened at age 40, or 10 years before the youngest case in your immediate family, whichever is earlier.
When Should I Get Tested?
If you have a family history of colon cancer, there are a number of genetic tests to find out if your cancer is hereditary, that is, caused by a genetic mutation passed down through the family. Your doctor can help you understand your individual cancer risk and which type of genetic tests, if any, may be useful for you or for other members of your family.
The most common types of hereditary colon cancer are familial adenomatous polyposis (FAP) and Lynch syndrome, also known as hereditary nonpolyposis colon cancer (HNPCC).
What is FAP Syndrome?
Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. People with the classic type of FAP may begin to develop multiple noncancerous (benign) growths (polyps) in the colon as early as their teenage years. The type of polyp most often seen in FAP syndrome, called an adenoma, is precancerous and has the potential to develop into cancer. Unless the growths are removed, these polyps may become malignant (cancerous). The average age at which an individual develops colon cancer in classic FAP is 39 years. Some people have a variant of the disorder, called attenuated familial adenomatous polyposis (AFAP), which develops fewer polyps. The average age of colon cancer onset for AFAP is 55 years.
In people with classic FAP, the number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon. Also of particular significance are noncancerous growths called desmoid tumors. These fibrous tumors usually occur in the tissue covering the intestines and may be provoked by surgery to remove the colon. Desmoid tumors tend to recur after they are surgically removed. In both classic FAP and AFAP, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin and other tissues. People who have colon polyps as well as growths outside the colon are sometimes described as having Gardner syndrome.
Approximately 2% of all colon cancer is thought to be caused by an adenomatous polyposis condition. They can be categorized into three conditions:
- Familial adenomatous polyposis (FAP)
- Attenuated familial adenomatous polyposis (AFAP)
- MYH-associated polyposis (MAP)
Classic familial adenomatous polyposis (FAP) and attenuated familial adenomatous polyposis (AFAP) are due to mutations in the adenomatous polyposis coli (APC) gene. MYH-associated polyposis (MAP) is caused by mutations in the mutY homolog (MYH) gene. Individuals with MAP have mutations in both of their MYH genes (one from each parent, often referred to as "biallelic MYH mutations"). Patients often have no family history of colon cancer or polyps in parents (although siblings may be affected).
When assessing hereditary cancer risk, a patient's personal and family history is collected to investigate the risk for a polyposis syndrome. Once a patient is identified as being at increased risk for one of these syndromes, genetic test results provide the most accurate means of cancer risk assessment for a patient. It is important to note that approximately 20% to 30% of FAP cases are caused by new mutations, meaning that an APC mutation may be present in an individual even if it is absent in both parents.
Also, due to the autosomal recessive inheritance pattern of MAP, many affected patients have no relatives with polyps or cancer. Genetic testing is the only way to identify truly at-risk family members.
Finding patients at risk for adenomatous polyposis syndromes and following up with them is perhaps the most critical step in changing hereditary cancer outcomes.
What is Lynch Syndrome?
In people with Lynch syndrome, a change or mutation in certain genes may allow the formation of small growths of tissue called polyps. Polyps in the colon are usually benign (noncancerous). However, the type of polyp most often seen in Lynch syndrome, called an adenoma, is precancerous and has the potential to develop into cancer. In Lynch syndrome these polyps can become cancerous more quickly than expected.
In the United States, about 160,000 new cases of colon cancer are diagnosed each year. Approximately 2-4% percent of these cancers are caused by Lynch syndrome. Doctors estimate that three out of every 100 colon cancers are caused by Lynch syndrome.
Inheriting a gene mutation ultimately puts you at higher risk. If one of your parents carries a Lynch syndrome gene mutation, you may carry this mutation also. The Lynch syndrome gene mutation can lead to an 82% risk of developing colon cancer by age 70. For women the gene can also lead to a 71% risk of developing endometrial cancer by age 70. Risks for other cancers, such as ovarian and stomach, are increased as well. The risk of colon cancer is dependent on which gene you carry a mutation in.
If you or a family member has a history of cancer, you should talk to your doctor about assessing your families’ risk for Lynch syndrome. Tests are available to help identify the genes, which indicate the presence of Lynch syndrome.